This application for a Mentored Patient-Oriented Research Career Award is designed to prepare the candidate for a career in patient-oriented research focused on co-occurring substance use and bipolar disorders, with a special emphasis on nicotine dependence. The candidate has a strong commitment to a research career and has demonstrated excellence in her clinical, administrative, and academic endeavors thus far. Her immediate career goals involve developing the skills and experience to secure independent research funding, with a long-term goal of making significant contributions to the understanding of the treatment of co-occurring substance use and bipolar disorders. MUSC is well-suited for this training, with an established and successful addictions research program and nationally-renowned mentors. The proposed training plan involves course work, supervised readings, and practical experience with leading experts. The candidate will study both basic science and clinical aspects of nicotine dependence, as well as co-morbid bipolar and substance use disorders. This unique integration of basic science and clinical implications will prepare the candidate to design and conduct scientifically-sound clinical research in individuals with both nicotine and bipolar disorders. The research project will integrate the candidate's clinical experience with co-morbid individuals with the development of strong research skills in pharmacological trials. Effective strategies have been developed for smoking cessation in the general population. Individuals with bipolar disorder, who are more likely to smoke than the general population, have been largely absent from smoking cessation trials. A number of studies have linked smoking cessation with the development of depressive symptoms; this is more likely in individuals with a prior history of depressive episodes, such as bipolar individuals. Thus, an antidepressant agent may be beneficial in smoking cessation in individuals with bipolar disorder. The proposed research project will test the hypothesis that sustained-release bupropion, an antidepressant and smoking cessation agent, is a safe and efficacious treatment for smoking cessation in bipolar smokers. The study will be a 10-week, randomized, double-blind, placebo-controlled trial evaluating sustained-release bupropion or placebo in combination with a behavioral intervention. Outcome will be measured by both self-report and biologic measures. The results of this study will provide preliminary data to guide future research in the area of nicotine dependence in bipolar disorder. Given the negative effects of smoking on general health, it is important to find successful treatments for smoking cessation. This study will enhance current understanding of treatments to help individuals with bipolar disorder quit smoking. [unreadable] [unreadable] [unreadable]